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OBJECTIVE: To establish optimal robust optimization uncertainty settings for clinical head and neck cancer (HNC) patients undergoing 3D image-guided pencil beam scanning (PBS) proton therapy.METHODS: We analyzed ten consecutive HNC patients treated with 70 and 54.25 GyRBE to the primary and prophylactic clinical target volumes (CTV) respectively using intensity-modulated proton therapy (IMPT). Clinical plans were generated using robust optimization with 5 mm/3% setup/range uncertainties (RayStation v6.1). Additional plans were created for 4, 3, 2 and 1 mm setup and 3% range uncertainty and for 3 mm setup and 3%, 2% and 1% range uncertainty. Systematic and random error distributions were determined for setup and range uncertainties based on our quality assurance program. From these, 25 treatment scenarios were sampled for each plan, each consisting of a systematic setup and range error and daily random setup errors. Fraction doses were calculated on the weekly verification CT closest to the date of treatment as this was considered representative of the daily patient anatomy.RESULTS: Plans with a 2 mm/3% setup/range uncertainty setting adequately covered the primary and prophylactic CTV (V95≥ 99% in 98.8% and 90.8% of the treatment scenarios respectively). The average organ-at-risk dose decreased with 1.1 GyRBE/mm setup uncertainty reduction and 0.5 GyRBE/1% range uncertainty reduction. Normal tissue complication probabilities decreased by 2.0%/mm setup uncertainty reduction and by 0.9%/1% range uncertainty reduction.CONCLUSION: The results of this study indicate that margin reduction below 3 mm/3% is possible but requires a larger cohort to substantiate clinical introduction.

BACKGROUND AND PURPOSE: Intensity-modulated proton therapy (IMPT) is expected to result in clinical benefits by lowering radiation dose to organs-at-risk (OARs). However, there are concerns about plan robustness due to motion. To address this uncertainty we evaluated the robustness of IMPT compared to the widely clinically used volumetric modulated arc therapy (VMAT) on weekly repeated computed tomographies (CT).MATERIALS AND METHODS: 19 patients with oesophageal cancer were evaluated. IMPT and VMAT plans were created on a planning 4-Dimensional CT (p4DCT) and evaluated on weekly repeated 4DCTs (r4DCT). In case of inadequate target coverage or unacceptable high dose to normal tissue, re-planning was performed. Dose distributions of the r4DCTs were warped to p4DCT, resulting in an estimated actual given dose (EAGD).RESULTS: Compared to VMAT, IMPT resulted in significantly lowered dose to heart, lungs, spleen, liver and kidneys. For IMPT, target coverage was adequate (after max 1 replanning) in 17/19 cases. In two cases target coverage remained insufficient. However, in one of these patients the summed dose was insufficient (due to tumor shrinkage) while weekly coverage was adequate. For the other patient the target coverage was also insufficient by VMAT, due to large anatomical changes during treatment. For VMAT, adequate target coverage was achieved in 18/19 cases without re-planning. However, for reasons of high OAR dose re-planning was required in two cases.CONCLUSION: IMPT reduces the dose to OARs significantly, while achieving adequate target coverage in the majority of patients. Re-planning was necessary for both IMPT and VMAT due to anatomical changes.

Background and purpose Non-small cell lung cancer (NSCLC) patients show typically large anatomical changes during treatment, making recalculation or adaption necessary. For report and review, the applied treatment dose can be accumulated on the reference planning CT using deformable image registration (DIR). We investigated the dosimetric impact of using six different clinically available DIR algorithms for dose accumulation in presence of inter-fractional anatomy variations. Materials and methods For seven NSCLC patients, proton treatment plans with 66 Gy-RBE to the planning target volume (PTV) were optimised. Nine repeated CTs were registered to the planning CT using six DIR algorithms each. All CTs were acquired in visually guided deep-inspiration breath-hold. The plans were recalculated on the repeated CTs and warped back to the planning CT using the corresponding DIRs. Fraction doses warped with the same DIR were summed up to six different accumulated dose distributions per patient, and compared to the initial dose. Results The PTV-V95 of accumulated doses decreased by 16% on average over all patients, with variations due to DIR selection of 8.7%. A separation of the dose effects caused by anatomical changes and DIR uncertainty showed a good agreement between the dose degradation caused by anatomical changes and the dose predicted from the average of all DIRs (differences of only 1.6%). Conclusion The dose degradation caused by anatomical changes was more pronounced than the uncertainty of employing different DIRs for dose accumulation, with averaged results from several DIRs providing a good representation of dose degradation caused by anatomy. However, accumulated dose variations between DIRs can be substantial, leading to an additional dose uncertainty., Radiotherapy & Oncology, 147, ISSN:0167-8140, ISSN:1879-0887

To optimize beam delivery and conformality of proton therapy, MRI integration has been proposed. Therefore, we investigated if proton irradiation in a magnetic field would change biological responses. Our data in cancer cell lines and stem cell-derived organoid models suggest that a magnetic field does not modify the biological response. (C) 2019 Elsevier B.V. All rights reserved.

Purpose/Objective Pencil beam scanning (PBS) is a highly conformal technology to treat cancer. The time structure of PBS makes the treatment of moving tumours challenging due to the interplay effect. According to literature, PBS in combination with rescanning can be safely applied without motion mitigation strategies to lung tumours that move 5 mm or less. However, the question is whether the motion measured during treatment simulation will remain below 5 mm during the course of treatment. We investigated the inter-fractional lung tumour motion variation in a unique data set providing five repeated 4DCTs per patient, to evaluate if a 5 mm threshold is a reliable indicator for considering PBS treatments. Material/Methods For 19 NSCLC patients (11 male, 8 female, age: 47-89, stage: II-IV) weekly 4DCT imaging was performed during treatment simulation before and during the treatment course to monitor the anatomical changes and differences in motion. Gross tumour volumes (GTV) were delineated on the maximum inspiration and expiration phases of the planning 4DCT and on the weekly repeat 4DCTs. GTV volume changes were acquired and the weekly inter-fraction motion variation was evaluated by measuring the GTV centroid translations in all three directions. Results The patients showed a median initial tumour motion of 1.3 mm (range: 0.0 – 5.1 mm) for a median initial GTV volume of 28.7 cm3 (range: 1.9 – 430.0 cm3). Figure 1 shows the measured 3D-vector motion for week 0 (before start treatment) and week 1-5 (treatment course). The maximum deviation from the initial measured motion for the patients was on average 2.1 mm (range: 0.3 – 7.9 mm). Centroid displacements remained under 5 mm for 16 out of 19 patients over the entire course of treatment. For patients number 3, 4 and 11, an increase in motion up to a maximum of respectively 9.1, 11.2, and 6.5 mm was observed (Figure 2). GTV volumes for 15 out of 19 patients shrank during treatment with a median decrease of 35.4% (range: 10.8% - 63.7%), and a median absolute volume change of 8.3 cm3 (range: 0.5 - 105.9 cm3). Conclusion Even if the lung tumour motion during planning simulation is under 5 mm, variations in motion amplitude and larger motions can still occur during the course of treatment. This indicates that the use of daily tumour motion evaluation is required for PBS treatments, especially for hypo-fractionated treatments. Future work will include a risk-stratification for motion variations in lung patients based on initial tumour motion, tumour position and tumour volume for different PBS spot sizes, time structure and prescribed treatment courses.